It is well known that substituted anilino-nicotinic acids and their salts are useful as analgesic anti-inflammatory agents. The preparation and properties of such compounds are well-known. See U.S. Pat. Nos. 3,337,570, 3,689,653 and 3,839,344 and Belgium Patent No. 679,271.
Flunixin, a substituted anilino-nicotinic acid derivative, is particularly, a potent analgesic in clinical and veterinary applications. Considering its potency and its lack of unwanted side effects, Flunixin is a more desirable analgesic than other drugs such as morphine, meperidine hydrochloride, and pentazocine. It is well established that doses of Flunixin such as 0.25 to 10 milligrams per kilogram of body weight administered parenterally (i.e. intravenously, subcutaneously or intramuscularly) result in a potent analgesic effect.
The known processes to prepare anilino-nicotinic acid derivatives typically involve condensing a 2-alkyl-3-perfluoroalkyl-aniline intermediate with a 2-chloronicotinic acid intermediate. Problems are associated with these processes, however. The processes provide low yields of product and the 2-alkyl-3-perfluoroalkyl-aniline intermediates are difficult to prepare and purify by conventional means. Furthermore, the preparations of those intermediates are generally accompanied by a variety of byproducts. For these reasons, the preparation of substituted anilino-nicotinic acid derivatives is an expensive process. Thus, it is an object of this invention to prepare the 2-alkyl-3-perfluoroalkyl-aniline intermediate by an economic synthetic route.